The process by which the body prevents blood loss is referred to as coagulation. Coagulation involves the formation of a blood clot (thrombus) that prevents further blood loss from damaged tissues, blood vessels or organs. This is a complicated process with a cellular system comprised of cells called platelets that circulate in the blood and serve to form a platelet plug over damaged vessels and a second system based upon the actions of multiple proteins (called clotting factors) that act in concert to produce a fibrin clot. These two systems work in concert to form a clot and disorders in either system can yield disorders that cause either too much or too little clotting.
Platelets serve three primary functions: (1) sticking to the injured blood vessel (a phenomenon called platelet adherence), (2) attaching to other platelets to enlarge the forming plug (a phenomenon called platelet aggregation), and (3) providing support for the processes of the coagulation cascade (molecules on the surface of platelets greatly accelerate several key reactions)
When a break in a blood vessel occurs, substances are exposed that normally are not in direct contact with the blood flow. These substances (primarily collagen and attached multimeric von Willibrand factor) allow the platelets to adhere to the broken surface. Once a platelet adheres to the surface, it releases chemicals that attract additional platelets to the damaged area, referred to as platelet aggregation. These two processes are the first responses to stop bleeding. The protein based system (the coagulation cascade) serves to stabilize the plug that has formed and further seal up the wound.
The support role of the platelet to the coagulation cascade is provided, in part, by one of the components on the outside of a platelet, called phospholipids, which are required for many of the reactions in the clotting cascade. The goal of the cascade is to form fibrin, which will form a mesh within the platelet aggregate to stabilize the clot. All of the factors have an inactive and active form. Once activated, the factor will serve to activate the next factor in the sequence until fibrin is formed. The coagulation cascade takes place at the site of a break in a blood vessel that has the platelet aggregate. Fibrin forms a mesh that, in concert with the platelets, plugs the break in the vessel wall. The fibrin mesh is then further stabilized by additional factors which cross-linkup the clot (much like forming an intricate network of reinforced strands of fibrin).
In the case of trauma induced bleeding, it is important to understand very quickly the clotting response of a particular individual in order to apply appropriate therapy to treat bleeding and ensure that the trauma is dealt with appropriately. Defective platelet functions, both primary (adhesive, von Willibrand factor interaction) and secondary (fibrin polymer organization and polymerization, integrin function) are recognized as a particularly important contributor in prolonged non-compressible bleeding. The development of hemostatic disorders in trauma patients, and associated progression in hemorrhagic and other shock states, can be due to different factors and thus require different therapies.
Currently, thromboelastography (TEG) is the accepted clinical standard for testing the efficiency of whole blood coagulation. For purposes of this disclosure, it should be noted that by “whole blood” is meant a mixture of whole blood with one or more substances, a fraction of whole blood containing one or more of the constituents of whole blood, a fraction of whole blood mixed with one or more non-blood substances, or a purified blood constituent, such as blood platelets or serum, a reconstituted blood preparation, a modified blood sample, or a blood substitute.
A TEG system was first developed in Germany in 1948 and has been incrementally improved since then. However, its principle of operation remains the same.
Traditional TEG requires a relatively large sample of blood, i.e., about 0.36 ml in a small cup. A pin is inserted into the blood and is rotated in a sinusoidal oscillation through a small angle at a low frequency. The device measures coupling of motion through rotation over time. It does not measure platelet adhesion, only polymerization of fibrin, and does not allow for mechanical activation of the coagulation response through shear forces. Thus, the information obtained from a TEG analysis falls far short of our current understanding of coagulation response, and requires excessive amounts of time which could result in inappropriate treatment for trauma being applied, leading to adverse results to a patient, possibly even death.
Another device generally known as the PFA-100 attempts to mimic a blood vessel by forcing blood flow through a narrow channel leading to a filter which has an aperture therein. The device measures the time for the aperture to clog and is essentially indicative of platelet function response which results in clogging. The time of closure of the aperture indirectly provides an indication of clotting due to platelet response. The use of such devices as TEG and the PFA-100 requires intensive laboratory training and upkeep, and they are not easily used in the field.
Accordingly, it is desirable to provide a portable coagulation monitoring device for diagnosis of trauma-related coagulopathies in the field, which yields rapid results, including extensive information about the complex mechanisms involved in coagulation, from a small sample of blood. More specifically, it is important to provide such a device which can be used by first responders under conditions encountered in the field, providing real time information, which allows for immediate treatment of a hemorrhaging event, as compared to prior art systems and devices which could result in delays of 45 minutes or more during what is considered an important initial time period for critical care to be applied and which use non-anticoagulated blood samples that do not have to be treated with activators and initiators as surrogates for the true coagulation process.